[Quality of life measures in oncology].
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Attitude to Health↗
Biomedical subjects
M Mercier
Publications and source records attributed to M Mercier.
Hydrolysis of retinyl esters in rat liver. Description of a lysosomal activity.
When incorporated into liposomes made of phospholipids, retinyl palmitate is an adequate substrate for an acidic REH (aREH). In rat liver, this activity is mainly localized in the lysosomal fraction. Kinetic parameters have been determined for retinyl palmitate (Km = 315 microM; maximal rate = 22.1 nmol retinol/h per mg protein). The aREH activity is different from the lysosomal acidic cholesteryl ester hydrolase (aCEH): cholesteryl oleate does not inhibit aREH activity, neither do some aCEH specific inhibitors, and aREH does not hydrolyse cholesteryl ester. Involvement of aREH in the hydrolysis of lipid droplets retinyl esters in fat storing cells is discussed.
Animals↗
Prognostic factors for autologous bone marrow transplantation in acute leukaemia: a single centre study of 105 patients.
Since the treatment of leukaemia by autologous bone marrow transplantation is becoming increasingly frequent, a retrospective study was undertaken to ascertain factors influencing the evolution of the disease (death and relapse). Data were collected over a period of 11 years for 105 patients with acute leukaemia (60 lymphoid cases and 45 myeloid cases). Multivariate analysis by the Cox model was used to determine prognostic factors for survival and disease free survival (DFS). Overall survival for the entire population was 35% after 8 years while DFS was 33% after 3 years. The major prognostic criteria were granulocyte recovery time (p < 0.001 at 5 weeks) and platelet recovery time (p < 0.02 at 6 weeks). Patients conditioned by an association of polychemotherapy and total body irradiation (TBI) showed a better survival rate than those conditioned by polychemotherapy alone (p < 0.01), with an overall survival of 48% after 3 years for the former group as compared to 19% for the latter. Other parameters influencing survival were the number of graft CFU-GM, sex and age. A knowledge of these factors could provide a means of predicting the long term evolution of leukaemia following autologous bone marrow transplantation. However, the present results require validation by a prospective study taking into account recent therapeutic protocols with haematopoietic growth factors.
Adolescent↗
Chemical risk evaluation.
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Chemical Industry↗
Effects of a long-interval retention on the hypoxia-induced impairment of performance in a fixed-interval schedule.
Retention of the fixed-interval (FI) responding was studied in rats after a chronic hypoxic treatment. The rats were trained over a 25-day period on a FI 60 s schedule. The rats were then given a normoxic or hypoxic (3.5% O2 for 10 min) treatment once a day for 4 days after which they were maintained in the animal quarters for 6 supplementary days. A retention test consisting of 4 daily FI 60 session followed the 10-day interval. The results showed that the performance during the retention test was very similar for both groups of rats. These data contrast with the deficit of retention observed when the retention FI 60 session were undertaken 24 h after the same hypoxic treatment. It is suggested that the results are due to a recovery from hypoxia-induced retrieval deficits rather than to the progressive attenuation of non-specific effects of hypoxia, such as anhedonia, hypoactivity, motivational changes or structural brain damage.
Amnesia, Retrograde↗
Measurement of hemoglobin and albumin adducts of benzo(a)pyrenediolepoxide and their rate of elimination in the female Sprague-Dawley rat.
A high performance liquid chromatographic technique coupled with fluorometric detection was used to study the disappearance rate of the hemoglobin and albumin adducts of benzo(a)pyrene (BaP) in female Sprague-Dawley rats. The technique was considered adequate based on good recovery (> 80%) of the analyte and satisfactory intra-assay coefficients of variations of 7.8% and 4.2% for hemoglobin and albumin adducts, respectively. The persistence of the adducts was determined in rats injected intravenously with 550 nmol BaP diolepoxide, the electrophilic metabolite of BaP. In a first experiment the isolated protein fractions were directly subjected to mild acid hydrolysis to yield the ultimate analyte, BaP tetrol. In a second experiment these fractions were first digested by proteases in order to liberate any unbound lipophilic BaP tetrol possibly "hidden" in the hydrophobic portions of the protein matrices. It was found that 70-100% of the measured tetrols originated from true adducts. The half-life of the free tetrol was 2.8 and 1.6 days in the hemoglobin and albumin fractions, respectively, compared to 10.7 and 3.6 days for the true adducts. Based on the total amount of tetrols, the mean half-life of the latter in the hemoglobin and albumin fractions determined from the two experiments was 9.0 and 2.7 days, respectively, assuming first order kinetics. The greater persistence of the hemoglobin adduct compared to that of the albumin adduct is coherent with the biological half-life of the intact proteins. However, the observed disappearance profile obtained does not fit with current models of adduct formation and removal.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Amineptine improves the performance of dogs in a complex temporal regulation schedule.
Amineptine is a tricyclic antidepressant with activating properties, that stimulates spontaneous locomotor activity in rodents and elevates mood in humans. It mainly inhibits dopamine uptake and weakly increased dopamine release. Formulating the hypothesis that this drug would decrease waiting capacity, we decided to test amineptine in a Differential Reinforcement of Response Duration schedule (DRRD 9 s Limited Hold 1.5 s) in the dog. The drug was administered orally at 2.5, 5.0, 7.5, 10 and 20 mg/kg, 1 h before the experimental session. Between 2.5 and 10 mg/kg, amineptine improved the performance by increasing the response (nonsignificantly) and reinforcement (significantly) rates and by increasing the peak of correct responses (significantly). The inverse effect was measured for the reinforcement rate (nonsignificantly) and for the peak of correct responses (significantly) at the dose of 20 mg/kg. These results were compared to those obtained with other classes of drugs, like neuroleptics, barbiturates or anxiolytics, that disturbed the performance, and particularly with low doses of neuroleptics, which also increase the dopamine release. The positive effects of amineptine on performance (2.5-10 mg/kg) were related to its inhibitory effect on dopamine uptake and discussed in terms of improved vigilance and attention, increase of waiting capacity, improved anticipation, and cognitive enhancement.
Animals↗
Differentiation of haloperidol and clozapine using a complex operant schedule in the dog.
This study aimed to differentiate chronically administered typical (haloperidol) and atypical (clozapine) neuroleptics in the dog using a complex temporal regulation schedule combining operant, voluntary, and involuntary motor parameters. Although clozapine and haloperidol showed some characteristics of neuroleptics, justifying their adherence to the same class of compounds, differences have also been highlighted and compared to the clinical observations. Haloperidol induced catalepsy, tremor, dystony, hyperkinesia, and stereotypy. Subjects produced anticipated responses before any stimulus. Incomplete and delayed responses were also produced. An interpretation in terms of akathisia and anhedonia has been suggested. Clozapine induced tremor, exploration, dystony, and hypersalivation. Subjects produced disinhibitory responses to the negative stimulus and incomplete responses but these latter were submitted to tolerance. The simultaneous presence of tranquilizing and disinhibitory effects has been reported on the clinical potential of clozapine both in cases of positive and negative schizophrenic symptomatologies.
Animals↗
Response to chemotherapy after relapse in patients with or without previous adjuvant chemotherapy for breast cancer. The French Epirubicin Study Group.
The French Epirubicin Study Group undertook a retrospective study to evaluate the response rate at relapse, time to treatment failure, and overall survival according to previous CMF-type adjuvant chemotherapy in patients who had taken part in two successive clinical trials. The statistical significance of the comparisons was tested after adjustment for the factors that differed most between the two groups. Patients who had received previous adjuvant chemotherapy had a lower response rate (p = 0.03), a shorter time to treatment failure (p = 0.007), and shorter overall survival after relapse (p = 0.008); overall survival after initial diagnosis was not significantly different. With respect to patients with axillary node metastases at the time of diagnosis (N+ patients), those with previous adjuvant chemotherapy had a lower response rate (p = 0.01) and shorter time to treatment failure (p = 0.02), but overall survival after relapse and after initial diagnosis were not significantly different. This retrospective and descriptive study suggests that chemotherapy is less effective after relapse, as measured by response rate and time to treatment failure, in patients with previous adjuvant chemotherapy.
Adult↗
Premenopausal patients with node-positive resectable breast cancer. Preliminary results of a randomised trial comparing 3 adjuvant regimens: FEC 50 x 6 cycles vs FEC 50 x 3 cycles vs FEC 75 x 3 cycles. The French Adjuvant Study Group.
Anthracyclines are among the most active drugs for the treatment of advanced breast cancer. Epirubicin has been found to be as effective as doxorubicin at equimolar doses but significantly better tolerated, especially in terms of alopecia, leucopenia, and cardiac toxicity. The role of anthracycline-containing regimens in adjuvant treatment of breast cancer has been studied by only a few clinical trial teams. In 1986, the French Adjuvant Study Group (FASG) began a randomised trial aimed to investigate the concept of dose intensity as well as the optimal duration of treatment in patients with early breast cancer. Between 1986 and 1990, 621 patients were included in the trial, of whom 595 were evaluable. Patients were randomised to 1 of 3 treatment groups: Group A (n = 207) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 6 cycles; Group B (n = 193) received FEC 50 every 21 days for 3 cycles; Group C (n = 195) received FEC 75 (fluorouracil 500 mg/m2, epirubicin 75 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 3 cycles. Locoregional radiotherapy was administered after the third cycle of chemotherapy in all treatment arms. Clinical prognostic factors were similar between treatment groups. Approximately 62% of all patients had 1 to 3 positive lymph nodes; 50% of patients were hormone receptor positive and 73% were Scarff-Bloom Richardson (SBR) grade 2 to 3. Toxicity was evaluated in 595 patients (207, 193 and 195 patients in Groups A, B and C, respectively), who received a total of 2301 chemotherapy cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Graft failure after T cell depleted HLA identical allogeneic bone marrow transplantation: risk factors in leukemic patients.
In a retrospective analysis of T cell depleted bone marrow transplantation, we have looked at different parameters in order to determine risk-factors of graft-failure after allogeneic bone marrow transplantation for leukemia. Fifty-one patients with acute leukemia or chronic myeloid leukemia have been analysed. For 33 of them, the pretransplant conditioning regimen consisted of fractionated total body irradiation (TBI) at 12 Gy prior to cyclophosphamide (120 mg/kg). The other patients received various reinforced preparative regimens. T-cell depletion consisted of treating marrow cells with pan-T monoclonal antibodies (CD2+CD3 or CD2-CD5-CD7) followed by complement mediated cytolysis. No post-transplant immunosuppressive prophylaxis was administered except for the first nine patients who received Methotrexate alone. In this group of 51 patients, 12 died within 3 months from graft-related complications and 10 developed graft failure (no engraftment or rejection). Among the possible risk factors associated with this failure, two graft-related parameters appeared significant: the number of CFU-GM progenitors and the number of viable T cells injected with the marrow inoculum. No correlation with graft failure was found with other parameters including diagnosis, disease status at transplant, conditioning regimen, age, sex, and CMV status of donor/host pairs. However, the interpretation must remain cautious because of the relatively small samples in each group.
Adolescent↗
Observation by transmission electron microscopy of etch figures obtained on an organic molecular crystal.
It is interesting to apply the method of etch figures to the study of organic molecular crystal defects, by observing the etch pits as soon as they are produced. We have set up a method to determine the geometrical forms of such small etch pits, observed on pre-shadowed replicas of naphthalene crystal surfaces. The described experimental procedure was designed to avoid artefacts due to vacuum sublimation and moisture traces on the replicated surface. Stereoscopic observation makes interpretation possible. The 3-D morphology and size of etch figures smaller than 1 micron can be determined.
Crystallography↗
Patient acceptance and differential perceptions of quality of life measures in a French oncology setting.
A three-part study evaluated French cancer patients' acceptance of self-rated quality of life measures, the predictive value of these measures, and the agreement between patient and health provider ratings of patient quality of life. In part one, 93% of 137 patients indicated a willingness to complete the Qualite de la Vie-Questionnaire (QOL-Q) and Analogues Lineaires pour la Mesure de la Qualite de vie (LA), and 63.6% indicated a willingness to be interviewed by a psychologist. Willingness to complete the scales was related to hospitalization status and treatment modality. In parts two and three, 100 patients were asked to complete the QOL-Q, LA, the Karnofsky Index (KI) and a side-effects checklist, and to undergo a psychological interview. Following interview, a psychologist rated the patients using the QOL-Q, and classified patient level of emotional distress. Oncologists rated the patient using the KI and the side-effects checklist. The results indicate that the patients' ratings of their quality of life were higher than the psychologist's ratings, and that the QOL-Q has predictive value in identifying severe emotional distress. Low level of patient and physician agreement on the KI was partially explained by patient age and cancer site. A moderate level of agreement was found between patient and physician perceptions of side effects. The study suggests that the QOL-Q, not the LA, may be useful as a screening tool to identify patients with impaired quality of life, and that self-rated measures should be included in quality of life assessments.
Adult↗
Polychlorinated and polybrominated biphenyl congeners and retinoid levels in rat tissues: structure-activity relationships.
The purpose of this study was to examine the structural requirements of polychlorinated and polybrominated biphenyls (PCBs and PBBs) for altering tissue levels of retinoids. Seven congeneric PCBs and PBBs were studied: 3,3',4,4'-tetrachlorobiphenyl (TCB), 2',3,3',4,5- and 3,3',4,4',5-pentachlorobiphenyls (-PeCBs), 3,3',4,4'- and 3,3',5,5'-tetrabromobiphenyls (-TBBs), 2,2',3,3',5,5'-hexachlorobiphenyl (-HCB), and 3,3',4,4',5,5'-hexabromobiphenyl (-HBB). Male Sprague-Dawley rats were fed a vitamin A-adequate diet (1.3 mg/kg) for 30 days before being given a single IP injection of one of seven polyhalogenated biphenyls (150 mumol/kg) in corn oil (10 ml/kg) or vehicle alone. Rats were killed 1 week later. Except for 3,3',4,4',5,5'-HBB, all PCBs and PBBs studied significantly decreased serum retinol levels and, except for 3,3',4,4',5,5'-HBB and 2,2',3,3',5,5'-HCB, all PCBs and PBBs also lowered the serum retinol-binding-protein (RBP) content. The activity of hepatic retinyl ester hydrolase (REH) was reduced by the treatment of 3,3',4,4',5-PeCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The levels of hepatic retinol were decreased by 2,2',3,3',5,5'-HCB, 2',3,3',4,5-PeCB, and 3,3',4,4',5-PeCB, while levels of hepatic retinyl palmitate were decreased by 2',3,3',4,5-PeCB, 3,3',4,4',5-PeCB, 3,3',4,4'-TCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The substantial decreases in hepatic retinyl palmitate levels could not be explained solely on the basis of hepatomegaly caused by acutely toxic PCBs and PBBs. All halogenated biphenyls which caused a decrease in hepatic retinyl palmitate also caused an increase in renal retinyl palmitate except 3,3',4,4',5-PeCB. In summary, the acutely toxic (nonortho substituted) congeners had pronounced effects on hepatic, renal, and serum retinoids whereas other biphenyls only decreased serum retinol levels. The effects of these seven compounds on REH activity were not correlated with the effects on serum retinol or RBP levels. Therefore, this study shows that the structure-activity relationships for altering hepatic retinoids differ from those for serum retinol, implying the involvement of multiple mechanisms.
Animals↗
Cancer incidence registration and trends in the Department of Doubs, France.
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Adolescent↗
[Soluble interleukin-2 receptor assay is unhelpful in chronic inflammatory rheumatism].
The level of soluble interleukin-2 receptors (SIL2-R), which reflects lymphocyte activation, is often described as a useful parameter for evaluating disease activity and progression in patients with inflammatory conditions. Serum SIL2-R was assayed using a sandwich ELISA method in 98 subjects including 38 controls (C), 36 patients with ankylosing spondylarthropathy (AS) and 24 patients with rheumatoid arthritis (RA). SIL2-R levels were higher in RA patients than in controls and AS patients (p < 10(-4)), whereas the difference between AS patients and controls was small (p = 0.02). In RA patients, SIL2-R levels were not correlated with any of the clinical or biological parameters studied and remained unchanged during clinical improvements. In the AS group, SIL2-R levels showed no correlations with inflammation parameters (CRP, IgA) and was similar in patients with and without HLA B27 or appendicular joint involvement. This study failed to provide any evidence that SIL2-R levels are helpful for monitoring patients with inflammatory joint disease.
Adult↗
[Recommendations for a comparison of techniques. Document F, stage 3].
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Autoanalysis↗
[Measurement of quality of life. Application to the screening of psychological distress in cancer patients].
As cancer treatments are becoming more and more traumatic the quality of life of these patients must be taken into consideration. This study was set up in 1982 and aimed at screening patients suffering from major psychological distress using a quantitative assessment of the quality of life. A self-administered questionnaire (QLQ) and linear analogues (LA) were developed and validated. The patient's acceptance of these two measuring instruments was tested on a sample group of patients in the Oncology Department of Besançon University Hospital and gave a result of 94% which was higher than that of a psychological interview (64%). A comparison of the assessment of the quality of life by the patient, the psychologist and the physician is an important phase in this concept. Agreement by the doctor and the patient using the Karnofsky indices was moderate (62% of the cases using a simplified scale): patients tended to overstate the extremes. The overall scores and the different questionnaire items completed by the patient and the psychologist were correlated, but agreement varied according to each item. An attempt was made to establish a predictive value for the questionnaire and the linear analogues to identify patients suffering from major psychological distress and requiring psychosocial support by comparing the results of the tests with the assessment of the psychologist during an interview. A stepwise logistical regression selected a combination of three items which screened more than 80% of these patients. The linear analogues were not sufficiently discriminatory to be used. The overall results suggest that a quality of life measurement can be integrated into daily clinical practice.
Humans↗